Stable Benzylic (1-Ethynylcyclohexanyl)carbonates Protect Hydroxyl Moieties by the Synergistic Action of [Au]/[Ag] Catalytic System

Article abstract of DOI:10.1021/acs.joc.9b00016

Chemical syntheses of oligosaccharides and glycosides call utilization of many protecting groups that can be installed or deprotected without affecting other functional groups present. Benzyl ethers are routinely used in the synthesis of glycans as they can be subjected to hydrogenolysis under neutral conditions. However, installation of benzyl ethers is often carried out under strong basic conditions using benzyl halides. Many a times, strongly basic conditions will be detrimental for some of the other sensitive functionalities (e.g., esters). Later introduced reagents such as benzyl trichloroacetimidate and BnOTf are not shelf-stable, and hence, a new method is highly desirable. Taking a cue from the [Au]/[Ag]-catalyzed glycosidations, we have identified a method that enables protection of hydroxyl groups as benzyl, p-methoxybenzyl, or naphthylenemethyl ethers using easily accessible and stable carbonate reagent. A number of saccharide-derived alcohols were subjected to the benzylation successfully using a catalytic amount of gold phosphite and silver triflate. Furthermore, the protocol is suitable for even protecting menthol, cholesterol, serine, disaccharide OH, and furanosyl-derived alcohol easily. The often-utilized olefins and benzoates, as well as benzylidene-, silyl-, Troc-, and Fmoc-protecting groups do not get affected during the newly identified protocol. Regioselective protection and one-pot installation of benzyl and p-methoxybenzyl ethers are demonstrated.

Full text of DOI:10.1021/acs.joc.9b00016

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Article
Stable Benzylic (1-Ethynylcyclohexanyl)carbonates Protect Hydroxyl
Moieties by The Synergistic Action of [Au]/[Ag]-catalytic System
Saptashwa Chakraborty, Bijoyananda Mishra, Mahesh Neralkar, and Srinivas Hotha
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00016 • Publication Date (Web): 03 May 2019
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Stable Benzylic (1-Ethynylcyclohexanyl)carbonates Protect Hydroxyl Moieties by The
Synergistic Action of [Au]/[Ag]-catalytic System
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Saptashwa Chakraborty, Bijoyananda Mishra, Mahesh Neralkar and Srinivas Hotha*
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Department of Chemistry, Indian Institute of Science Education and Research
Pune – 411 008, India
s.hotha@iiserpune.ac.in
Abstract:
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Chemical syntheses of oligosaccharides and glycosides call utilization of many protecting
groups which can be installed or deprotected without affecting other functional groups present.
Benzyl ethers are routinely used in the synthesis of glycans as they can be subjected to
hydrogenolysis under neutral conditions. However, installation of benzyl ethers is often carried
out under strong basic conditions using benzyl halides. Many a times, strongly basic
conditions will be detrimental for some of the other sensitive functionalities (e.g. esters). Later
introduced reagents such as benzyl trichloroacetimidate and BnOTf are not shelf-stable and
hence, a new method is highly desirable. Taking a cue from the [Au]/[Ag]-catalyzed
glycosidations, we have identified a method that enables protection of hydroxyl groups as
benzyl, p-methoxy benzyl or naphthylenemethyl ethers using easily accessible and stable
carbonate reagent. A number of saccharide derived alcohols were subjected to the
benzylation successfully using catalytic amount of gold-phosphite and silver triflate.
Furthermore, the protocol is suitable for even protecting menthol, cholesterol, serine,
disaccharide-OH and furanosyl derived alcohol easily. Often utilized Benzylidene-, silyl-,
olefins, benzoates, Troc- and Fmoc-, protecting groups do not get affected during the newly
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identified protocol. Regioselective protection and one-pot installation of benzyl and p-methoxy
benzyl ethers is demonstrated.
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Introduction:
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Chemical glycosidation is a condensation reaction involving a glycosyl donor and an acceptor
which will be repeatedly utilized while synthesizing oligosaccharides. Chemical synthesis of
oligosaccharides is still a challenging task as regioselectivity among multiple reactive alcohols
is highly demanding.1 Often, the glycosyl donor and the acceptor are protected in order to
reduce undesirable competition among similarly reactive alcohols.2 Often, glycosyl donors are
prepared in a fully protected form with a leaving group at the C-1 position whereas the
acceptor (ROH) is synthesized in such a way that a lone hydroxyl group is left for undergoing
the glycosylation. Facile syntheses of large and branched oligosaccharides generally exploit
protection and deprotection strategies on demand.3,4
Several decades of research culminated into the development of chemistry for the protection
and/or deprotection of alcohols.5 Benzylation of alcohols to afford benzyl ethers is one of the
most celebrated reactions that many oligosaccharide syntheses utilize.
Frequently,
benzylations are conducted under NaH/DMF/benzyl halides conditions which are strongly
alkaline and hence, base-labile protecting groups also get affected.6 Later introduced BnOTf7
permits benzylation under neutral conditions whereas benzyl trichloroacetimidates8a-d enable
syntheses of benzyl ethers under acid catalysis using catalytic amount of TfOH. A gold-
catalyzed microwave assisted synthesis of unsymmetrical ethers using alcohols as alkylating
agents was recently reported by Liu et al.8e However, moisture sensitivity and instability of
BnOTf and benzyl trichloroacetamidates are the major limitations of these two methods.8
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Therefore, installation of benzylic ethers under mild catalytic conditions that provide excellent
yields will be highly rewarding.
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Results and Discussion
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Recently, glycosyl (1-ethynylcyclohexyl)carbonates (e.g. 1) were identified as glycosyl donors
under the synergistic catalytic action of Au-phosphite (2) and AgOTf to afford the glycosides 3
with the extrusion of the spirocyclic carbonate 4.9 The reaction was postulated to undergo
through the activation of alkyne by the [Au]/[Ag]-catalytic system resulting in the formation of a
carbocation at the C-1 position extruding the Au-alkylidene B.9 Thus formed carbocation is
highly stabilized due to the formation of the oxocarbenium ion intermediate A1 which will be in
equilibrium with the trioxolenium ion intermediate A2 (Scheme 1). Attack of the aglycon ROH
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AuCl
Previous Work:
t-Bu
t-Bu
t-Bu
O P O
O
t-Bu
t-Bu
6
7
8
9
OBz
O
O
O
OBz
2
t-Bu
ROH
+
+
BzO
BzO
O
OR
O
O
BzO
BzO
AgOTf, CH2Cl2
4Å MS powder, 15 min, 85-98%
OBz
O
OBz
O
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1
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Glycosylation
Protodeauration
..
ROH
..
AuL
O
O
O
O
Intermediates
O
+
(BzO)3
(BzO)3
O
O
O
O
Ph
Ph
A1
A2
B
R1
Hypothesis:
OH
O
O
BzO
BzO
O
O
BzO
O
2
(5 mol%)
OCH3
O
AgOTf(10 mol%)
BzO
7
B
+
BzO
4
R1
+
Protection
CH2Cl2, 4Å MS powder
0.5-1.0 h
R1 = -OCH3
BzO
OCH3
A3
R1
Nu:
8
9
R1 = -OCH3
R1 = -H
5
6
R1 = -H
R1 = OCH3
TMSN3
N3
4
+
H3CO
C
N3 Asymmetric vibration at 2095 cm-1(IR)
Scheme 1: Benzylic (1-ethynylcyclohexyl)carbonates for the synthesis of benzylic ethers
led to glycosides and the protodeauration resulted in the formation of the spirocyclic carbonate
4. Push of electrons from the exo-cyclic oxygen is envisaged as one of the possible factors for
the stabilization of the carbocation at the anomeric position. In this scenario, we hypothesized
that the benzylic carbonates shall also undergo similar reaction to afford benzylic cation A3
releasing the intermediate B and thus formed benzylic cation shall be available for the attack of
nucleophiles. To verify our hypothesis, benzylic carbonates 5 and 6 were respectively
prepared from commercially available 4-methoxy benzyl alcohol and benzyl alcohol in
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excellent yields using easily accessible and stable 1-ethynylcyclohexyl (4-nitrophenyl)
carbonate.9
A model reaction was carried out between glucose-derived alcohol 7 and the
6
7
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9
carbonate 5 in the presence of 4Å MS powder, 5mol% of Au-phosphite (2) and 10mol% of
AgOTf at 25 ⁰C to obtain corresponding PMB-ether 8 in 95% yield and the cyclic carbonate 4.
Similar reaction with benzyl (1-ethynylcyclohexyl)carbonate 6 with alcohol 7 afforded the
benzyl protected monosaccharide 9 in 84% yield. Gratifyingly, the benzoate esters were found
to be intact during the reaction, the reaction was complete in 30min and most importantly, the
benzylic carbonate is noticed to be very stable. Formation of the benzylic cation A3 was
established by conducting the reaction with the TMSN3 instead of alcohol 7 to afford the 4-
methoxy benzyl azide (C) and the cyclic carbonate 4. Azide formation was confirmed by the
characteristic N3 asymmetric vibration at 2095 cm-1.10a
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A plausible mechanism can be advanced based on the literature precedence though a
thorough mechanistic investigation is pending (Figure 1).9 p-Methoxy benzyl carbonate 5 can
be activated either by the in situ formed LAuOTf to give intermediate A4 or by the sub-
stoichiometric [Au,Ag] clusters to give intermediate A5. Intermediates A4 and A5 undergo
1,5-exo-dig cyclization giving the earlier postulated alkylidene intermediate B releasing the
much desired benzylic carbocation A6 that shall be attacked by the alcohol 7 to give PMB-
ether 8 releasing a proton that facilitates the protodeauration to give the cyclic carbonate 4.10b,c
It might also be possible to obtain the product 8 by concerted bimolecular substitution reaction
releasing the alkylidene B due to the attack of the nucleophile 7.10b,c
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MeO
O
O
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O
LAuCl
AgOTf
AgCl
5
Path
a
LAuOTf
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Path
b
O
O
O
[Au,Ag]
O
4
O
O
..
..
A5
AuL
MeO
O
H
O
AuL
O
..
MeO
O
O
A4
..
O
B
MeO
OH
O
A6
BzO
BzO
7
BzO
OCH3
H
OPMB
O
BzO
BzO
BzO
OCH3
8
Figure 1. Plausible mechanism
Encouraged by the identification of the new benzylation protocol, we further targeted the
application of this method for the synthesis of benzyl ethers to understand the substrate scope.
Accordingly, it has been noticed that olefins do not get affected under these experimental
conditions as evident while perform reactions on alcohols 10,11a 12,11b 1411c to obtain
corresponding PMB-ethers 11,13,15. Noticeably, the Troc-protection on the glucosamine
derivative 12 and the silyl ethers in compounds 12 and 13 were stable for these conditions. In
addition, the current procedure is suitable for installation of benzyl ethers on alcohols which
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are alicyclic (e.g. menthol 16), steroidal (e.g. cholesterol 18), amino acid (e.g. serine 2011d) to
afford respectively PMB-ethers 17, 19 and 21 in very high yields (Chart 1). Furthermore, the
reaction is found to be suitable for installation of PMB ethers or benzyl ethers on disaccharide
(e.g. 2211e), benzylidene glucoside (e.g 24, 2611f) and furanoside 283 to give respective ethers
23,25,27,29.
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OTBDPS
OBn
O
OBn
O
R1O
BnO
BnO
O
O
R1O
TBDPSO
R1O
BzO
BzO
O
NHTroc
O
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R1 = H
R1 = PMB
R1 = H
R1 = PMB
R1 = H
R1 = PMB
96%
85%
78%
H
O
R1O
H
H
R1O
OBn
NHFmoc
R1O
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17
18
19
20
21
R1 = H
R1 = PMB
R1 = H
R1 = PMB
R1 = H
R1 = PMB
81%
84%
90%
R1O
BzO
O
R1O
O
Ph
O
Ph
BzO
O
O
O
O
O
O
R1O
R1O
BzO
OBz
O
R1O
BzO
O
OCH3
OCH3
OBz
O
OBz
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23
24
25
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27
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29
R1 = H
R1 = PMB
R1 = H
R1 = PMB
R1 = H
R1 = Bn
R1 = H
R1 = Bn
94%
92%
72%
75%
Chart 1: Substrate Scope
Another benzyl ether in the form of Nap-ethers gained momentum as their deprotection
conditions are orthogonal to the benzyl ethers.12 In view of this, alcohol 7 was treated with
Nap-carbonate 30 in the presence of catalytic quantities of Au-phosphite (2) and AgOTf in
CH2Cl2 to notice formation of Nap-ether 31 in 62% yield. Similarly, arabinofuranosyl alcohols
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323 and 333 reacted with carbonate 30 to afford desired Nap-ethers 34 and 35 in 55% and 58%
5
6
yield respectively (Scheme 2).
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9
O
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2
(5 mol%)
ONap
O
O
O
AgOTf(10 mol%)
BzO
BzO
7
CH2Cl2, 4Å MS powder
1 h, 62%
+
BzO
OCH3
30
31
2
(5 mol%)
R1O
O
R1O
O
HO
NapO
AgOTf(10 mol%)
+
30
CH2Cl2, 4Å MS powder
1 h
O
O
OR2
OR2
32
33
34
35
R1 = Bz, R2 = Bn
R1 = Bn, R2 = Bn
R1 = Bz, R2 = Bn (55%)
R1 = Bn, R2 = Bn (58%)
Scheme 2: Synthesis of Nap-ethers
1⁰-Alcohols are better nucleophiles than 2⁰-alcohols and as a consequence, the attack of the
nucleophile on the benzylic cation shall also follow the same trend. Hence, easily accessible
allyl glucoside 3611c possessing both primary and secondary alcohols was subjected to the
benzylation conditions using PMB-carbonate 5 in the presence of catalyst 2 and AgOTf in
CH2Cl2 to notice formation of the C6-PMB blocked glucoside 37 in 75% yield. In continuation,
the PMB ether 37 was subjected to identical conditions with Bn-carbonate 6 to afford the
benzyl ether 38 in 52% of isolated yield. All the reaction conditions are identical except the
substrates and hence, a one pot conversion of diol 36 to compound 38 was envisioned so that
the purification is minimized and overall pot-economy shall improve as a result. Accordingly,
the two independent reactions are conducted one after the other in one pot without isolating
the intermediate compound 37 to obtain the final compound 38 in 45% over all isolated yield
(Scheme 3).
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One pot (45% Yield))
4
5
6
7
8
5
OH
6
OPMB
O
OPMB
O
2
(5 mol%), AgOTf (10 mol%)
2
(5 mol%), AgOTf (10 mol%)
O
HO
BzO
HO
BzO
BnO
BzO
CH2Cl2, 4Å MS powder
1 h, 52%
CH2Cl2, 4Å MS powder
BzO
BzO
O
O
BzO
O
1 h, 0 C 75%
9
36
37
38
10
11
12
13
14
Scheme 3: PMB and Bn ethers can be introduced orthogonally and in one pot as well
To summarize, a new method for the installation of benzyl-, 4-methoxy benzyl- and Nap-
ethers has been identified taking cue from the [Au]/[Ag]-catalyzed alkynyl carbonate
glycosylation chemistry. These conditions are mild enough to synthesize benzyl ethers
bearing olefins, silyl ethers, Troc-, Fmoc-, benzyl esters, benzoates, and benzylidenes. The
mechanism was postulated to be similar to that of the alkynyl glycosyl carbonate glycosidation.
One pot installation of PMB and benzyl ethers is yet another new feature of the current
protocol.
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Experimental Section
General Methods. Unless otherwise noted, materials were obtained from commercial
suppliers and were used without further purification.1-Ethynylcyclohexanol, p-nitrophenyl
chloroformate, menthol (16), cholesterol (18), Compound 24 and all metal salts were
purchased from Sigma-Aldrich. Unless otherwise reported all reactions were performed under
Nitrogen atmosphere. Removal of solvent in vacuo refers to distillation using a rotary
evaporator attached to an efficient vacuum pump. Products obtained as solids or syrups were
dried under high vacuum. Analytical thin-layer chromatography was performed on pre-coated
silica plates (F254, 0.25 mm thickness); compounds were visualized by UV light or by staining
with anisaldehyde spray. IR spectra were recorded on a FT-IR spectrometer. NMR spectra
were recorded either on a 400 or a 500 MHz with CDCl3 as the solvent and TMS as the
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internal standard. High resolution mass spectroscopy (HRMS) was performed using an ESI-
TOF mass analyser. Low resolution mass spectroscopy (LRMS) was performed on UPLC-MS
with SWADESI-TLC interface.
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1-Ethynylcyclohexyl (4-methoxybenzyl) carbonate (5): DMAP (2.65 g, 21.71 mmol) was
added to a CH2Cl2 (20 mL) solution of p-methoxybenzyl alcohol (1.77 mL, 14.48 mmol) and
stirred for 30 min. 1-Ethynylcyclohexyl 4-nitrophenyl carbonate (5.03 g, 17.37 mmol) was
added in three portions (3x1.7 g) in 30 min intervals. The reaction mixture was stirred for 3 h,
concentrated in vacuo to obtain the crude residue that was purified by silica gel column
chromatography using 5% ethyl acetate-hexane as mobile phase to obtain compound 5 (3.97
g, 95% yield) as a white crystalline solid.
1-Ethynylcyclohexyl (benzyl) carbonate (6): DMAP (2.03 g, 16.65 mmol) was added to a
CH2Cl2 (15 mL) solution of benzyl alcohol (1.13 mL, 11.10 mmol) and stirred for 30 min. 1-
Ethynylcyclohexyl 4-nitrophenyl carbonate (3.85 g, 13.32 mmol) was added in three portions
(3x1.3 g) in 30 min intervals. The reaction mixture was stirred for 3 h, concentrated in vacuo to
obtain the crude residue that was purified by silica gel column chromatography using 2% ethyl
acetate-hexane as mobile phase to obtain compound 6 (2.7 g, 94% yield) as a white crystalline
solid.
1-Ethynylcyclohexyl (napthalen-2-yl methyl) carbonate (30): DMAP (1.16 g, 16.65 mmol)
was added to a CH2Cl2 (10 mL) solution of 2-napthalenemethanol (1.00 g, 6.32 mmol) and
stirred for 30 min. 1-Ethynylcyclohexyl 4-nitrophenyl carbonate (2.19 g, 7.6 mmol) was added
in three portions (3x700 mg) in 30 min intervals. The reaction mixture was stirred for 3 h,
concentrated in vacuo to obtain the crude residue that was purified by silica gel column
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chromatography using 2% ethyl acetate-hexane as mobile phase to obtain compound 30 (2.7
4
5
6
g, 94% yield) as a white amorphous solid.
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Procedure for 1-(azidomethyl)-4-methoxybenzene synthesis (C): A solution of carbonate 5
(50 mg, 1 equiv) in CH2Cl2 (2 mL) was treated with excess trimethylsilyl azide (300 µL) and
freshly activated 4Å molecular sieves powder, stirred for 15 min. Gold-phosphite catalyst 2
(7.62 mg, 0.05 equiv) and AgOTf (4.45 mg, 0.10 equiv) was added and stirred for 1 h.
Preparative TLC was performed to avoid compound loss due to the high volatile nature of
azide C.
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General procedure of the gold-catalyzed PMB-ether preparation: To a solution of alcohol
(7,10,12,14,16,18,20,22, or 24) (1.0 equiv) and the carbonate 5 (1.0 equiv per –OH group) in
anhydrous CH2Cl2 (3 mL/100 mg of alcohol) was added freshly activated 4Å MS powder (30
mg/mL) and stirred for 20 minutes under nitrogen atmosphere. To the reaction mixture at 25
oC, gold-phosphite 2 (5 mol%) and AgOTf (10 mol%) were added and stirred for 30 minutes.
At the end of the reaction as adjudged by the TLC examination, the reaction mixture was
passed through a bed of celite and the filtrate was concentrated in vacuo to obtain a residue
that was purified by silica gel column chromatography using ethyl acetate and hexane as
mobile phase.
This procedure was adopted for the synthesis of compounds 8,11,13,15,17,19,21,23, and 25.
General procedure of the gold-catalyzed Benzyl ether preparation: To a solution of
alcohol (7, 26 or 28) (1.0 equiv) and the carbonate 6 (1.2 equiv per –OH group) in anhydrous
CH2Cl2 (3 mL/100 mg of alcohol) was added freshly activated 4Å MS powder (30 mg/mL) and
stirred for 20 min under nitrogen atmosphere. To the reaction mixture at 25 oC, gold-phosphite
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2 (5 mol%) and AgOTf (10 mol%) were added and stirred for 1 h. At the end of the reaction as
adjudged by the TLC examination, the reaction mixture was passed through a bed of celite and
the filtrate was concentrated in vacuo to obtain a residue that was purified by silica gel column
chromatography using ethyl acetate and hexane as mobile phase.
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This procedure was adopted for the synthesis of compounds 9, 27 and 29.
General procedure of the gold-catalyzed Nap-ether preparation: Alcohol (7, 32 or 33) (1.0
equiv) was dissolved in anhydrous CH2Cl2 (3 mL/ 100 mg alcohol) and freshly activated 4Å MS
powder (30 mg/mL) was added and stirred for 15 min. Gold-phosphite 2 (5 mol%) and AgOTf
(10 mol%) were added to the reaction mixture under nitrogen atmosphere. A solution of
carbonate 30 (1.5 equiv per –OH group) in dry CH2Cl2 was added dropwise and slowly and
o
stirred for 1 h at 25 C. At the end of the reaction as adjudged by the TLC examination, the
reaction mixture was passed through a bed of celite and the filtrate was concentrated in vacuo
to obtain a residue that was purified by silica gel column chromatography using ethyl acetate
and hexane as mobile phase.
This procedure was adopted for the synthesis of compounds 31, 34 and 35.
Procedure for selective primary PMB-ether protection: Alcohol (36) (170 mg, 0.4 mmol)
was dissolved in anhydrous CH2Cl2 (5 mL/100 mg alcohol, to maintain the higher dilution
percentage) and freshly activated 4Å MS powder was added and stirred for 20 min. Gold-
phosphite 2 (10 mol%) and AgOTf (10 mol%) were added to the reaction mixture under
nitrogen atmosphere. A solution of carbonate 5 (0.3 equiv, 38 mg) in 0.5 mL of dry CH2Cl2
⁰
was added dropwise and slowly at 0 C and this process was repeated for three more times
with addition of 150 mg of carbonate 5 (1.2 equiv, 0.52 mmol) in total and stirred for 30 min at
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0 C. At the end of the reaction as adjudged by the TLC examination, the reaction mixture was
passed through a bed of celite and the filtrate was concentrated in vacuo to get a residue that
was purified by silica gel column chromatography using ethyl acetate:hexane (8:92) as mobile
phase to obtain compound 37 as a gum (134 mg, 75% yield).
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Procedure for one-pot synthesis of PMB and Bn-ethers: Selective PMB protection was
performed on alcohol 36 (120 mg) by following above delineated procedure. In the same pot,
gold-phosphite 2 (5 mol%) and AgOTf (10 mol%) were added afterwards. Next, a solution of
carbonate 6 (2 equiv dissolved in 1 mL of dry CH2Cl2) was added in a slow dropwise manner
under inert atmosphere. The progress of the reaction was monitored by TLC examination, after
the completion of the reaction, the mixture was passed through a bed of celite and the filtrate
was concentrated in vacuo to obtain a residue that was purified by silica gel column
chromatography using ethyl acetate and hexane as mobile phase obtaining compound 38 in
an overall yield of 45% (50 mg).
Characterization Data
1-Ethynylcyclohexyl 4-methoxybenzyl carbonate (5): White crystalline solid, mp (⁰C): 56-59, IR
(cm-1, CHCl3): 3264, 2938, 2860,1746,1447,1269, 1077, 911, 730, 578; 1H NMR (400.31 MHz,
CDCl3): δ 1.20 – 1.37 (ddq, J = 13.7, 9.3, 4.7 Hz, 1H), 1.45 – 1.55 (m, 1H), 1.54 – 1.73 (m,
4H), 1.77 – 1.91 (dt, J = 10.5, 4.0 Hz, 2H), 2.16 (dt, J = 10.5, 4.0 Hz, 2H), 2.62 (s, 1H), 3.77 (s,
3H), 5.07 (s, 2H), 6.83 – 6.88 (m, 2H), 7.28 – 7.33 (m, 2H); 13C{1H} NMR (100.67 MHz, CDCl3):
δ 22.6, 22.6, 25.1, 36.9, 36.9, 55.3, 69.2, 74.9, 77.6, 83.1, 114.0, 114.0, 127.5, 130.4, 130.4,
152.9, 159.9; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H20O4Na 311.1259; Found
311.1262.
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1-Ethynylcyclohexyl benzyl carbonate (6): Crystalline solid, mp (⁰C): 59-63; IR (cm-1, CHCl3):
5
6
1
3266, 2932, 2861, 1746, 1514, 1448,1231, 1077, 971, 788, 555; H NMR (400.31 MHz,
7
8
9
CDCl3): δ 1.31 (ddq, J = 13.7, 9.3, 4.7 Hz, 1H), 1.46 – 1.58 (m, 1H), 1.57 – 1.74 (m, 4H), 1.86
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(dt, J = 10.5, 4.0 Hz, 2H), 2.18 (dt, J = 10.5, 4.0 Hz, 2H), 2.63 (s, 1H), 5.15 (s, 2H), 6.89 – 7.75
13
(m, 5H); C{1H} NMR (100.67 MHz, CDCl3): δ 22.6, 22.6, 25.1, 36.9, 36.9, 69.3, 75.0, 77.7,
83.1, 128.5, 128.5, 128.5, 128.6, 128.5, 135.4, 152.9; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd
for C16H18O3Na 281.1154; Found 281.1151.
1-(azidomethyl)-4-methoxybenzene (C):
Liquid; IR (cm-1, CHCl3): 2922,2851,2095
(N3),1611,1513,1461; 1H NMR (400.31 MHz, CDCl3): δ 3.84 (s, 3H), 4.29 (s, 2H), 6.94 (d, J =
8.7 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H); HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C8H9N3ONa
186.0643; Found 186.0638.
Methyl 2,3,4-tri-O-benzoyl-6-O-(p-methoxybenzyl) α-D-glucopyranoside (8):
Eluent for
purification: 15% ethyl acetate in n-hexane; yield 117 mg from 100 mg of compound 7 (95%);
Thick syrup; [α]25 (CHCl3, c 1.5): +68.9⁰; IR (cm-1, CHCl3): 2925, 2852, 1727, 1512, 1451,
D
1366, 1249, 1098, 1033, 754, 707 ; 1H NMR (400.31 MHz, CDCl3). δ 3.50 (s, 3H), 3.62 – 3.71
(m, 2H), 3.75 (s, 3H), 4.25 (ddd, J = 10.2, 4.5, 2.9 Hz, 1H), 4.44 – 4.58 (m, 2H), 5.26 – 5.34
(m, 2H), 5.68 (t, J = 9.9 Hz, 1H), 6.15 (t, J = 9.6 Hz, 1H), 6.74 – 6.80 (m, 2H), 7.20 – 7.26 (m,
2H), 7.27 – 7.35 (m, 2H), 7.36 – 7.48 (m, 5H), 7.50 – 7.57 (m, 2H), 7.87 – 8.03 (m, 6H);13C{1H}
NMR (100.67 MHz, CDCl3): δ 55.2, 55.6, 68.1, 68.9, 69.5, 70.7, 72.2, 73.3, 97.0, 113.7, 113.7,
128.3, 128.3, 128.3, 128.3, 128.4, 128.4, 129.1, 129.2, 129.3, 129.5, 129.5, 129.7, 129.7,
129.7, 129.8, 129.8, 129.9, 129.9, 133.0, 133.2, 133.3, 159.1, 165.2, 165.8, 165.8; HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C36H34O10Na 649.2050; Found 649.2059.
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Methyl 2,3,4-tri-O-benzoyl-6-O-benzyl α-D-glucopyranoside (9): Eluent for purification: 15%
4
5
6
ethyl acetate in n-hexane; yield 150 mg from 147 mg of compound 8 (84%); Thick syrup; [α]25
D
7
8
9
(CHCl3, c 0.5): +37.6⁰; IR (cm-1, CHCl3): 3890, 3738, 2924, 2857, 1730, 1600, 1452, 1366,
1273, 1173, 1042, 917, 710 ; 1H NMR (400.31 MHz, CDCl3): δ 3.34 (s, 3H), 3.54 (t, J = 3.8 Hz,
2H), 4.10 (dt, J = 7.6, 4.5 Hz, 1H), 4.42 (dd, J = 12.0, 10.2 Hz, 2H), 5.08 – 5.19 (m, 2H), 5.52
(t, J = 9.9 Hz, 1H), 6.00 (t, J = 9.5 Hz, 1H), 7.02 – 7.18 (m, 7H), 7.19 – 7.30 (m, 5H), 7.35 –
7.39 (m, 2H), 7.73 – 7.78 (m, 4H), 7.84 – 7.85 (m, 2H); 13C{1H} NMR (100.67 MHz, CDCl3): δ
55.7, 68.7, 69.0, 69.6, 70.7, 72.2, 73.8, 97.1, 127.7, 127.8, 127.8, 128.3, 128.3, 128.4, 128.4,
128.4, 128.4, 128.5, 128.5, 129.2, 129.2, 129.4, 129.8, 129.8, 129.9, 129.9, 130.0, 130.0,
133.1, 133.3, 133.4, 137.7, 165.3, 165.9, 165.9; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C35H32O9Na 619.1944; Found 619.1940.
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Pent-4-enyl 2,3,4-tri-O-benzyl-6-O-(p-methoxybenzyl) α-D-mannopyranoside (11): Eluent for
purification: 15% ethyl acetate in n-hexane; yield 177 mg from 150 mg of compound 10 (96%);
Syrup; [α]25 (CHCl3, c 0.9): +10.2⁰; IR (cm-1, CHCl3): 2925, 1738, 1738, 1610, 1511, 1453,
D
1
1365, 1216, 1096, 910, 818, 697; H NMR (400.31 MHz, CDCl3): δ 1.65 (q, J = 6.9 Hz, 2H),
2.09 (q, J = 6.7 Hz, 2H), 3.40 (dt, J = 9.7, 6.4 Hz, 1H), 3.68 – 3.74 (m, 2H), 3.76 – 3.82 (m,
6H), 3.93 (dd, J = 9.4, 3.0 Hz, 1H), 3.99 – 4.04 (m, 1H), 4.49 (d, J = 3.7 Hz, 1H), 4.52 (d, J =
2.7 Hz, 1H), 4.63 – 4.66 (m, 3H), 4.73 – 4.80 (m, 2H), 4.89 (s, 1H), 4.90 (d, J = 10.6 Hz, 1H),
4.93 – 5.07 (m, 2H), 5.81 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 6.84 – 6.87 (m, 2H), 7.13 – 7.21 (m,
2H), 7.26 – 7.36 (m, 10H), 7.36 – 7.44 (m, 5H); 13C{1H} NMR (100.67 MHz, CDCl3): δ 28.7,
30.4, 55.3, 67.0, 68.9, 71.9, 72.3, 72.7, 73.1, 74.9, 75.1, 75.3, 80.4, 98.0, 113.8, 113.8, 115.0,
127.7, 127.7, 127.7, 127.8, 127.8, 128.0, 128.0, 128.1, 128.1, 128.4, 128.4, 128.4, 128.5,
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128.5, 128.5, 129.6, 129.6, 130.6, 138.2, 138.6, 138.6, 138.7, 159.2; HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for C40H46O7Na 661.3141; Found 661.3146.
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8
9
Allyl 2-deoxy-2-(((2,2,2-trichloroethoxy)carbonyl)amino)-3-O-benzoyl-4-O-(p-methoxybenzyl)-
6-O-(tert-butyldiphenylsilyl) β-D-glucopyranoside (13): Eluent for purification: 20% ethyl acetate
in n-hexane; yield 136 mg from 143 mg of compound 12 (85%); Yellow syrup; [α]25D (CHCl3, c
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1
1.0): +30.8⁰; IR (cm-1, CHCl3): 2933, 1738, 1516, 1367, 1216, 1105, 1036, 707; H
NMR(400.31 MHz, CDCl3): δ 1.16 (s, 9H), 3.72 (s, 3H), 3.88 (ddd, J = 9.9, 3.8, 2.0 Hz, 1H),
3.93 – 4.00 (m, 3H), 4.04 (ddt, J = 12.8, 6.4, 1.3 Hz, 1H), 4.17 – 4.26 (m, 2H), 4.50 – 4.59 (m,
3H), 4.73 (d, J = 12.0 Hz, 1H), 5.02 (d, J = 3.6 Hz, 1H), 5.24 (dd, J = 10.4, 1.4 Hz, 1H), 5.32
(dq, J = 17.2, 1.6 Hz, 1H), 5.44 (d, J = 10.1 Hz, 1H), 5.67 (dd, J = 10.8, 9.1 Hz, 1H), 5.92
(dddd, J = 17.0, 10.4, 6.4, 5.3 Hz, 1H), 6.64 – 6.67 (m, 2H), 6.94 – 6.99 (m, 2H), 7.41 – 7.50
(m, 8H), 7.57 – 7.63 (m, 1H), 7.78 (m, 4H), 8.06 – 8.11 (m, 2H);13C{1H} NMR (100.67 MHz,
CDCl3): δ 19.4, 26.9, 26.9, 26.9, 54.6, 55.1, 62.6, 68.2, 72.1, 74.1, 74.3, 74.6, 75.7, 95.3, 96.3,
113.7, 118.2, 127.6, 127.6, 127.8, 127.8, 128.4, 128.4, 129.6, 129.7, 129.7, 129.7, 129.7,
129.7, 129.7, 129.9, 129.9, 133.1, 133.2, 133.4, 133.6, 135.7, 135.7, 135.9, 135.9, 154.4,
159.2, 166.4; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C43H48O9NCl3SiNa 878.2062 Found
878.2059.
Allyl
2-O-benzoyl-3-O-tert-butyldiphenylsilyl-4-O-(p-methoxybenzyl)-6-O-benzyl
α-D-
glucopyranoside (15): Eluent for purification: 15% ethyl acetate in n-hexane; yield 80 mg from
74 mg of compound 14 (78%); Solid, mp (⁰C): 170-172; [α]25D (CHCl3, c 1.0): +104.6⁰; IR (cm-1,
CHCl3): 2929, 2858,1726, 1610, 1513, 1454, 1367, 1246, 1160, 1105, 927, 822, 741, 610; 1H
NMR (400.31 MHz, CDCl3): δ 0.95 (s, 9H), 3.70 – 3.80 (m, 2H), 3.82 – 3.87 (m, 5H), 3.88 –
3.93 (m, 1H), 4.01 – 4.08 (m, 1H), 4.48 (d, J = 10.6 Hz, 1H), 4.59 (d, J = 12.1 Hz, 1H), 4.64 –
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4.74 (m, 2H), 4.80 (d, J = 10.6 Hz, 1H), 4.97 (dt, J = 10.5, 1.3 Hz, 1H), 5.01 – 5.10 (m, 2H),
5.13 (dd, J = 3.9, 1.3 Hz, 1H), 5.64 (ddt, J = 16.0, 10.4, 5.2 Hz, 1H), 6.75 – 6.90 (m, 2H), 6.93
– 7.03 (m, 2H), 7.10-7.17 (m, 2H), 7.18 – 7.26 (m, 3H), 7.31 – 7.38 (m, 4H), 7.39 – 7.51 (m,
7H), 7.53-7.63 (m, 2H), 7.70-7.81 (m, 2H); 13C{1H} NMR (100.67 MHz, CDCl3): δ 19.6, 26.8,
26.8, 26.8, 55.3, 68.0, 68.7, 70.0, 73.5, 73.6, 73.7, 74.7, 78.9, 94.9, 113.6, 113.6, 116.5, 127.2,
127.2, 127.5, 127.5, 127.6, 127.6, 127.8, 128.0, 128.0, 128.5, 128.5, 129.0, 129.0, 129.1,
129.5, 129.7, 129.7, 129.7, 130.6, 132.4, 133.4, 133.6, 133.9, 135.3, 135.3, 136.0, 136.0,
138.0, 159.0, 165.9; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C47H52O8SiNa 795.3329; Found
795.3332.
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1-((((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)-4-methoxybenzene (17): Eluent
for purification: 10% ethyl acetate in n-hexane; yield 78 mg from 55 mg of compound 16 (81%);
Liquid; [α]25 (CHCl3, c 1.0): -74.5; IR (cm-1, CHCl3): 3882,2951, 2922, 2865, 1739, 1612,
D
1513, 1456, 1369, 1246, 1040, 820, 591; 1H NMR (400.31 MHz, CDCl3): δ 0.70 (d, J = 6.9 Hz,
3H), 0.86 (s, 1H), 0.89 (s, 3H), 0.92 (s, 3H), 0.94 – 0.98 (m, 1H), 1.26 (s, 3H), 1.59 – 1.67 (m,
2H), 2.22 (d, J = 46.8 Hz, 2H), 3.11 – 3.18 (m, 1H), 3.79 (s, 3H), 4.33 (d, J = 11.1 Hz, 1H),
4.58 (d, J = 11.1 Hz, 1H), 6.86 (d, J = 6.6 Hz, 2H), 7.26 (d, J = 8.7 Hz, 2H);13C{1H} NMR
(100.67 MHz, CDCl3): δ 16.0, 21.0, 22.4, 23.2, 25.5, 31.6, 34.6, 40.3, 48.3, 55.2, 70.0, 78.4,
113.7, 113.7, 129.3, 129.3, 131.2, 159.0; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C18H28O2Na 299.1987 Found: 299.1992.
O-(p-methoxybenzyl)cholesterol (19): Eluent for purification: 10% ethyl acetate in n-hexane;
yield 220 mg from 200 mg of compound 18 (84%); Pale brown solid, mp (⁰C): 109-111; [α]25
D
(CHCl3, c 1.0): -16.3⁰; IR (cm-1, CHCl3): 2937, 2861, 1737, 1512, 1459, 1369, 1245, 1099,
1035, 818, 526; 1H NMR (400.31 MHz, CDCl3): δ 0.71 (s, 3H), 0.87 – 0.98 (m, 10H), 1.04 (s,
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3H), 1.10-1.17 (m, 7H), 1.27 – 1.43 (m, 6H), 1.46 – 1.64 (m, 7H), 1.82 – 2.10 (m, 5H), 2.29
(ddd, J = 13.5, 11.0, 2.8 Hz, 1H), 2.44 (ddd, J = 13.3, 4.8, 2.3 Hz, 1H), 3.29 (tt, J = 11.2, 4.5
Hz, 1H), 3.82 (s, 3H), 4.52 (s, 2H), 5.37 (dt, J = 5.5, 1.9 Hz, 1H), 6.88 – 6.93 (m, 2H), 7.27 –
13
7.33 (m, 2H); C{1H} NMR (100.67 MHz, CDCl3): δ 11.9, 18.8, 19.4, 21.1, 22.6, 22.9, 23.9,
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24.3, 28.0, 28.3, 28.5, 31.9, 32.0, 35.8, 36.2, 36.9, 37.3, 39.2, 39.5, 39.8, 42.3, 50.2, 55.3,
56.2, 56.8, 69.6, 78.3, 113.8, 113.8, 121.5, 129.2, 129.2, 131.2, 141.0, 159.0; HRMS (ESI-
TOF) m/z: [M+Na]+ Calcd for C35H54O2Na 529.4022; Found 529.4023.
Benzyl N-(((9H-fluoren-9-yl)methoxy)carbonyl)-O-(p-methoxybenzyl)-L-serinate (21): Eluent for
purification: 25% ethyl acetate in n-hexane; yield 140 mg from 105 mg of compound 20 (90%);
Yellow solid; mp (⁰C): 97-100; [α]25D (CHCl3, c 1.0): -0.1⁰; IR (cm-1, CHCl3): 3441, 3208, 2953,
1728, 1513, 1452, 1364, 1297, 1243, 1036, 744, 528 ; 1H NMR (400.31 MHz, CDCl3): δ 3.76
(dd, J = 9.6, 3.0 Hz, 1H), 3.82 (s, 3H), 3.97 (dt, J = 9.6, 2.9 Hz, 1H), 4.29 (t, J = 7.3 Hz, 1H),
4.46 (m, 4H), 5.18 – 5.33 (m, 2H), 5.81 – 5.93 (m, 1H), 6.90 (dd, J = 8.7, 2.6 Hz, 2H), 7.21 (dd,
J = 8.6, 2.6 Hz, 2H), 7.33 – 7.41 (m, 7H), 7.46 (t, J = 7.5 Hz, 2H), 7.68 (dt, J = 7.7, 3.9 Hz, 2H),
7.82 (d, J = 7.6 Hz, 2H); C{1H} NMR (100.67 MHz, CDCl3): δ 47.2, 54.6, 55.3, 67.3, 69.5,
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73.0, 113.9, 113.9, 120.0, 120.0, 125.2, 125.3, 127.1, 127.2, 127.8, 127.8, 128.2, 128.2, 128.4,
128.4, 128.6, 128.6, 129.4, 129.4, 129.5, 135.4, 141.3, 141.3, 143.8, 144.0, 156.1, 159.4,
170.4; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C33H31O6NNa 560.2049; Found 560.2051.
4-pentenyl
2,3-di-O-benzoyl-5-O-[2,3-di-O-benzoyl-5-O-(p-methoxybenzyl)-α-D-
arabinofuranosyl]-α-D-arabinofuranoside (23): Eluent for purification: 20% ethyl acetate in n-
hexane; yield 270 mg from 250 mg of compound 22 (94%); Yellow solid; mp (⁰C): 167-170;
[α]25D (CHCl3, c 1.0): +0.4⁰; IR (cm-1, CHCl3): 3888, 3828, 3393, 2927, 1724, 1605, 1258, 1176,
1107, 1032, 914, 711, 525 ; 1H NMR (400.31 MHz, CDCl3): δ 1.73 – 1.82 (m, 2H), 2.16 – 2.23
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(m, 2H), 3.54 (dt, J = 9.5, 6.1 Hz, 1H), 3.78 (s, 3H), 3.79 – 3.91 (m, 3H), 3.96 (dd, J = 11.1, 3.1
Hz, 1H), 4.24 (dd, J = 11.2, 4.6 Hz, 1H), 4.49 (td, J = 4.7, 3.0 Hz, 1H), 4.59 – 4.66 (m, 3H),
4.98 (ddt, J = 10.2, 2.2, 1.3 Hz, 1H), 5.03 (dq, J = 17.1, 1.7 Hz, 1H), 5.23 (s, 1H), 5.45 (s, 1H),
5.50 – 5.54 (m, 2H), 5.62 (d, J = 1.2 Hz, 1H), 5.64 – 5.67 (m, 1H), 5.84 (ddt, J = 16.9, 10.2, 6.7
Hz, 1H), 6.78 – 6.86 (m, 2H), 7.26 – 7.34 (m, 4H), 7.38 – 7.54 (m, 8H), 7.56 – 7.63 (m, 2H),
7.94 – 8.11 (m, 8H); 13C{1H} NMR (100.67 MHz, CDCl3): δ 28.7, 30.3, 55.2, 66.2, 66.6, 69.2,
73.2, 77.7, 77.7, 81.5, 81.7, 81.8, 82.5, 105.6, 105.9, 113.7, 113.7, 114.9, 128.2, 128.2, 128.4,
128.4, 128.4, 128.4, 128.4, 128.4, 129.0, 129.2, 129.2, 129.3, 129.3, 129.3, 129.8, 129.8,
129.8, 129.8, 129.8, 129.8, 129.9, 129.9, 130.0, 133.1, 133.3, 133.3, 133.4, 138.1, 159.1,
165.1, 165.4, 165.6, 165.7; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C51H50O14Na 909.3098;
Found 909.3094.
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Methyl 2,3-di-O-(p-methoxybenzyl)-4,6-O-benzylidene α-D-glucopyranoside (25): Eluent for
purification: 15% ethyl acetate in n-hexane; yield 85 mg from 50 mg of compound 24 (92%);
Thick syrup; [α]25 (CHCl3, c 0.5): +44.9⁰; IR (cm-1, CHCl3): 3070, 2890, 1682, 1533, 1450,
D
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1265, 1216, 1090, 917, 839; H NMR (400.31 MHz, CDCl3): δ 3.38 (s, 3H), 3.51 (dd, J = 9.3,
3.7 Hz, 1H), 3.57 (t, J = 9.4 Hz, 1H), 3.69 (t, J = 10.2 Hz, 1H), 3.78 (s, 3H), 3.78 (t, J = 10.2 Hz,
1H), 3.79 (s, 3H), 4.00 (t, J = 9.3 Hz, 1H), 4.25 (dd, J = 10.0, 4.7 Hz, 1H), 4.53 (d, J = 3.7 Hz,
1H), 4.62 (d, J = 11.9 Hz, 1H), 4.72 – 4.86 (m, 3H), 5.53 (s, 1H), 6.73 – 6.99 (m, 4H), 7.20 –
7.34 (m, 4H), 7.37 (d, J = 7.0 Hz, 3H), 7.46 – 7.53 (m, 2H); 13C{1H} NMR (100.67 MHz,
CDCl3): δ 55.2, 55.3, 55.3, 62.4, 69.1, 73.4, 75.0, 78.3, 78.7, 82.1, 99.3, 101.3, 113.7, 113.7,
113.8, 113.8, 126.1, 126.1, 128.2, 128.2, 128.9, 129.7, 129.7, 129.8, 129.8, 130.3, 130.9,
137.5, 159.2, 159.4; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C30H34O8Na 545.2151; Found
545.2147.
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Methyl 2-O-benzoyl-3-O-benzyl-4,6-O-benzylidene α-D-glucopyranoside (27): Eluent for
purification: 20% ethyl acetate in n-hexane; yield 221 mg from 250 mg of compound 26 (72%);
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White solid; mp (⁰C): 135-139; [α]25 (CHCl3, c 1.0): +128.2⁰; IR (cm-1, CHCl3): 3020, 2923,
D
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1722, 1271, 1214, 1098, 996, 745, 668, 580 ; 1H NMR (400.31 MHz, CDCl3): δ 3.42 (s, 3H),
3.85 (q, J = 9.7, 9.2 Hz, 2H), 3.97 (td, J = 9.8, 4.6 Hz, 1H), 4.25 (t, J = 9.3 Hz, 1H), 4.38 (dd, J
= 10.1, 4.6 Hz, 1H), 4.79 – 4.95 (m, 2H), 5.11 (d, J = 3.8 Hz, 1H), 5.16 (ddd, J = 9.5, 3.8, 0.8
Hz, 1H), 5.67 (s, 1H), 7.19 – 7.25 (m, 3H), 7.26 – 7.30 (m, 2H), 7.41 – 7.52 (m, 5H), 7.54 –
7.59 (m, 2H), 7.60 – 7.66 (m, 1H), 8.07 – 8.11 (m, 2H);13C{1H} NMR (100.67 MHz, CDCl3): δ
55.4, 62.4, 69.0, 73.6, 74.8, 75.8, 82.3, 98.0, 101.4, 126.1, 126.1, 127.6, 128.0, 128.0, 128.3,
128.3, 128.3, 128.3, 128.4, 128.4, 129.0, 129.7, 130.0, 130.0, 133.3, 137.4, 138.2, 166.0;
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C28H28O7Na 499.1733; Found 499.1739.
4-pentenyl 2,3-di-O-benzoyl-5-O-benzyl α-D-arabinofuranoside (29): Eluent for purification:
15% ethyl acetate in n-hexane; yield 92 mg from 100 mg of compound 28 (75%); Syrup; [α]25
D
(CHCl3, c 1.0): -18.8⁰; IR (cm-1, CHCl3): 2927, 1725, 1600, 1451, 1362, 1264, 1108,1067,
1029, 710; 1H NMR (400.31 MHz, CDCl3): δ 1.70 – 1.80 (m, 2H), 2.14 – 2.24 (m, 2H), 3.55 (dt,
J = 9.5, 6.2 Hz, 1H), 3.78 – 3.85 (m, 1H), 3.85 – 3.95 (m, 2H), 4.43 – 4.50 (m, 1H), 4.67 (s,
2H), 4.97 (ddd, J = 10.1, 2.0, 1.1 Hz, 1H), 5.02 (dq, J = 17.2, 1.7 Hz, 1H), 5.26 (s, 1H), 5.48 (d,
J = 1.3 Hz, 1H), 5.52 (d, J = 4.8 Hz, 1H), 5.83 (ddt, J = 16.9, 10.1, 6.6 Hz, 1H), 7.24 – 7.32 (m,
3H), 7.34 – 7.42 (m, 4H), 7.42 – 7.48 (m, 2H), 7.53 – 7.61 (m, 2H), 7.97 – 8.03 (m, 2H), 8.06 –
8.10 (m, 2H); 13C{1H} NMR (100.67 MHz, CDCl3): 28.9, 30.4, 66.8, 69.9, 73.8, 77.9, 81.9, 82.4,
105.8, 115.0, 127.7, 127.8, 127.8, 128.5, 128.5, 128.5, 128.5, 128.6, 128.6, 129.3, 129.5,
130.0, 130.0, 130.0, 130.0, 133.5, 133.5, 138.1, 138.2, 165.5, 165.9; HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for C31H32O7Na 539.2046; Found 539.2045.
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1-ethynylcyclohexyl (naphthalen-2-ylmethyl) carbonate (30): White amorphous solid; mp (⁰C):
59-62; IR (cm-1, CHCl3): 3290, 2940, 2863, 1770, 1593, 1493, 1268, 1206, 1008, 771; 1H NMR
(400.31 MHz, CDCl3): δ 1.23 – 1.40 (m, 1H), 1.49 – 1.58 (m, 1H), 1.59 – 1.75 (m, 4H), 1.82 –
1.93 (m, 2H), 2.15 – 2.24 (m, 2H), 2.64 (d, J = 1.4 Hz, 1H), 5.32 (s, 2H), 7.44 – 7.54 (m, 3H),
7.80 – 7.89 (m, 4H); 13C{1H} NMR (100.67 MHz, CDCl3): 22.6, 22.7, 25.1, 36.9, 36.9, 69.5,
75.0, 77.8, 83.1, 126.0, 126.4, 126.4, 127.7, 127.8, 128.2, 128.5, 132.8, 133.3, 133.3, 152.9;
HRMS (ESI-TOF) m/z: M+ Calcd for C20H20O3 308.1412; Found 308.1412.
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Methyl 2,3,4-tri-O-benzoyl-6-O-(naphthalene-2-ylmethyl) α-D-glucopyranoside (31): Eluent for
purification: 12% ethyl acetate in n-hexane; yield 119 mg from 150 mg of compound 7 (62%);
Syrup; [α]25 (CHCl3, c 1.0): +55.9⁰; IR (cm-1, CHCl3): 2924, 2855, 1728, 1600, 1452, 1366,
D
1269, 1171, 1100, 1041, 974, 857, 756, 711; 1H NMR (400.31 MHz, CDCl3): δ 3.53 (s, 3H),
3.78 (t, J = 3.8 Hz, 2H), 4.31 (dt, J = 7.6, 4.5 Hz, 1H), 4.77 (dd, J = 12.0, 10.2 Hz, 2H), 5.32 –
5.39 (m, 2H), 5.75 (t, J = 9.9 Hz, 1H), 6.20 (t, J = 9.5 Hz, 1H), 7.31 – 7.55 (m, 12H), 7.73 –
7.80 (m, 4H), 7.90 – 7.94 (m, 4H), 8.03 – 8.04 (m, 2H); 13C{1H} NMR (100.67 MHz, CDCl3): δ
55.6, 68.6, 68.9, 69.6, 70.7, 72.2, 73.8, 97.1, 125.8, 125.8, 126.0, 126.7, 127.7, 127.9, 128.2,
128.3, 128.3, 128.3, 128.3, 128.4, 128.4, 129.1, 129.1, 129.3, 129.7, 129.7, 129.7, 129.7,
130.0, 130.0, 133.0, 133.1, 133.2, 133.2, 133.4, 135.1, 165.3, 165.9, 165.9; HRMS (ESI-TOF)
m/z: [M+Na]+ Calcd for C39H34O9Na 669.2101; Found 669.2097.
4-pentenyl 2-O-benzoyl-3-O-benzyl-5-O-naphthalene-2-ylmethyl α-D-arabinofuranoside (34):
Eluent for purification: 15% ethyl acetate in n-hexane; yield 74 mg from 100 mg of compound
32 (55%); Liquid; [α]25 (CHCl3, c 1.0): +51.3⁰; IR (cm-1, CHCl3): 3019, 2923, 2858, 1816,
D
1723, 1453, 1264, 1215, 1106, 816, 746, 669 ; 1H NMR (400.31 MHz, CDCl3): δ 1.69 – 1.79
(m, 2H), 2.11 – 2.21 (m, 2H), 3.51 (dt, J = 9.7, 6.4 Hz, 1H), 3.64 (dd, J = 10.7, 5.1 Hz, 1H),
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3.72 (dd, J = 10.7, 3.6 Hz, 1H), 3.79 (dt, J = 9.7, 6.6 Hz, 1H), 4.03 (d, J = 5.5 Hz, 1H), 4.35 (td,
J = 5.3, 3.7 Hz, 1H), 4.58 (d, J = 12.1 Hz, 2H), 4.71 (q, J = 12.2 Hz, 1H), 4.80 (d, J = 12.1 Hz,
1H), 4.96 (ddd, J = 11.4, 2.2, 1.3 Hz, 1H), 5.04 (dd, J = 17.1, 1.8 Hz, 1H), 5.18 (s, 1H), 5.38 (d,
J = 1.4 Hz, 1H), 5.83 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 7.19 – 7.27 (m, 3H), 7.28 – 7.33 (m,
4H), 7.38 (dd, J = 8.4, 1.6 Hz, 1H), 7.44 – 7.53 (m, 3H), 7.71 – 7.76 (m, 3H), 7.79 – 7.83 (m,
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1H), 7.92 – 7.97 (m, 2H); C{1H} NMR (100.67 MHz, CDCl3): δ 28.8, 30.3, 67.0, 69.5, 72.3,
73.6, 82.1, 82.1, 83.5, 106.2, 114.9, 125.8, 126.0, 126.2, 126.6, 127.8, 127.8, 128.0, 128.0,
128.0, 128.2, 128.4, 128.4, 128.5, 128.5, 129.5, 129.8, 129.8, 133.1, 133.3, 133.4, 135.5,
137.8, 138.3, 165.6; HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C35H36O6Na 575.2410; Found
575.2411.
4-pentenyl 2,3-di-O-benzyl-5-O-naphthalene-2-ylmethyl α-D-arabinofuranoside (35): Eluent for
purification: 12% ethyl acetate in n-hexane; yield 86 mg from 73 mg of compound 33 (58%);
Liquid; [α]25 (CHCl3, c 0.5): +39.6⁰; IR (cm-1, CHCl3): 2923, 2863, 1738, 1366, 1213, 1099,
D
909, 744, 699; 1H NMR (400.31 MHz, CDCl3): δ 1.71 – 1.79 (m, 2H), 2.14 – 2.23 (m, 2H), 3.48
(qd, J = 6.6, 3.3 Hz, 1H), 3.71 (tdd, J = 10.9, 8.4, 4.5 Hz, 2H), 3.81 (dtd, J = 9.8, 6.5, 3.3 Hz,
1H), 4.00 (dt, J = 6.9, 3.5 Hz, 1H), 4.08 (dd, J = 3.4, 1.5 Hz, 1H), 4.25 – 4.32 (m, 1H), 4.50 –
4.57 (m, 2H), 4.61 (dd, J = 11.9, 3.3 Hz, 2H), 4.78 (t, J = 3.6 Hz, 2H), 5.02 (dq, J = 10.3, 1.5
Hz, 1H), 5.05 – 5.13 (m, 2H), 5.88 (dqd, J = 16.9, 6.7, 3.4 Hz, 1H), 7.28 (tq, J = 7.5, 3.9, 3.1
Hz, 5H), 7.37 (d, J = 3.1 Hz, 5H), 7.51 (ddd, J = 8.9, 5.2, 2.3 Hz, 3H), 7.80 – 7.90 (m, 4H);
13C{1H} NMR (100.67 MHz, CDCl3): δ 28.8, 30.4, 67.0, 69.8, 72.0, 72.2, 73.5, 80.5, 83.6, 88.5,
106.2, 114.9, 125.9, 125.9, 126.1, 126.6, 127.7, 127.7, 127.8, 127.8, 127.9, 127.9, 127.9,
127.9, 128.2, 128.3, 128.3, 128.5, 128.5, 133.0, 133.3, 135.6, 137.6, 137.9, 138.3; HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C35H38O5Na 561.2617; Found 561.2620.
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Allyl 2,3,-di-O-benzoyl-6-O-(p-methoxybenzyl) α-D-glucopyranoside (37): white solid, mp (⁰C):
153-156; [α]25D (CHCl3, c 1.0): +140.6⁰; IR (cm-1, CHCl3): 3497, 2922, 1725, 1609, 1513, 1453,
1275, 1103, 1037, 712, 562; 1H NMR (400.31 MHz, CDCl3): δ 3.23 (s, 1H), 3.75 – 3.89 (m,
5H), 3.97 – 4.11 (m, 3H), 4.27 (ddt, J = 13.3, 5.1, 1.6 Hz, 1H), 4.59 (q, J = 11.7 Hz, 2H), 5.16
(dq, J = 10.4, 1.4 Hz, 1H), 5.28 – 5.36 (m, 3H), 5.80 – 5.84 (m, 1H), 5.85 – 5.92 (m, 1H), 6.89
– 6.95 (m, 2H), 7.28 – 7.34 (m, 2H), 7.35 – 7.41 (m, 4H), 7.49 – 7.55 (m, 2H), 7.99 – 8.03 (m,
4H); 13C{1H} NMR (100.67 MHz, CDCl3): δ 55.3, 68.6, 69.2, 70.5, 70.6, 71.4, 73.4, 74.1, 95.3,
113.9, 113.9, 117.6, 128.4, 128.4, 128.4, 128.4, 129.2, 129.4, 129.4, 129.8, 129.9, 129.9,
129.9, 129.9, 129.9, 133.3, 133.3, 133.5, 159.3, 166.0, 167.2; HRMS (ESI-TOF) m/z: [M+Na]+
Calcd for C31H32O9Na 571.1944; Found 571.1945.
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Allyl 2,3,-di-O-benzoyl-4-O-benzyl-6-O-(p-methoxybenzyl) α-D-glucopyranoside (38): Thick
syrup [α]25 (CHCl3, c 1.0): +164.4⁰; IR (cm-1, CHCl3): 2966, 1725, 1615, 1508, 1480, 1134,
D
1037, 712, 533; 1H NMR (400.31 MHz, CDCl3): δ 3.70 – 3.74 (m, 1H), 3.82 (s, 3H), 3.85 (dd, J
= 10.8, 2.7 Hz, 1H), 4.00 – 4.06 (m, 3H), 4.23 (ddt, J = 13.2, 5.1, 1.6 Hz, 1H), 4.44 – 4.56 (m,
3H), 4.68 (d, J = 11.7 Hz, 1H), 5.13 (dd, J = 10.4, 1.5 Hz, 1H), 5.22 (dd, J = 10.2, 3.7 Hz, 1H),
5.29 (dd, J = 17.2, 1.7 Hz, 1H), 5.32 (d, J = 3.8 Hz, 1H), 5.80 – 5.87 (m, 1H), 6.04 – 6.09 (m,
1H), 6.90 – 6.93 (m, 2H), 7.03 (dd, J = 6.6, 2.8 Hz, 2H), 7.13 – 7.18 (m, 3H), 7.28 (s, 1H), 7.32
13
– 7.36 (m, 2H), 7.37 – 7.40 (m, 3H), 7.49 – 7.53 (m, 2H), 7.97 – 8.00 (m, 4H); C{1H} NMR
(100.67 MHz, CDCl3): δ 55.3, 67.7, 68.5, 70.3, 72.2, 72.8, 73.3, 74.7, 76.0, 95.3, 113.9, 113.9,
117.5, 127.7, 127.7, 128.0, 128.0, 128.2, 128.2, 128.3, 128.3, 128.4, 128.4, 129.3, 129.7,
129.7, 129.8, 129.8, 129.9, 129.9, 133.0, 133.2, 133.5, 137.5, 139.3, 159.4, 165.7, 166.0;
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C38H38O9Na 661.2414; Found 661.2412.
ASSOCIATED CONTENT
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Supporting Information
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Spectral charts. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
s.hotha@iiserpune.ac.in
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Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENTS
SC and BM, MN acknowledges research fellowship from IISER Pune and CSIR-UGC-NET
respectively.
SH
thanks
financial
assistance
from
DBT-New
Delhi
(BT/PR20820/MED/30/1875/2017). Authors thank Sandip Pasari for fruitful discussions.
References
1. (a) Nielsen, M. M.; Pedersen, C. M., Catalytic Glycosylations in Oligosaccharide
Synthesis, Chem. Rev. 2018, 118, 8285-8358; (b) Panza, M.; Pisorio, S. G; Stine, K. J.;
Demchenko, A. V., Automated Chemical Oligosaccharide Synthesis: Novel Approach to
Traditional Challenges, Chem. Rev. 2018, 118, 8105-8150.
2. (a) Seeberger, P. H.; Werz, D. B., Synthesis and Medical Applications of
Oligosaccharides, Nature 2007, 446, 1046-1051; (b) Zhu, X.; Schmidt, R. R., New
Principles for Glycoside-bond Formation, Angew. Chem. Int. Ed. 2009, 48, 1900-1934.
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TOC Figure:
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Stable Benzylic (1-Ethynylcyclohexanyl)carbonates Protect Hydroxyl Moieties by The
Synergistic Action of [Au]/[Ag]-catalytic System
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